Probing the folding of mini-protein Beta3s by two-dimensional infrared spectroscopy; simulation study

Abstract

We propose to use infrared coherent two-dimensional correlation spectroscopy (2DCS) to characterize the folding mechanism of the mini-protein Beta3s. In this study Beta3s was folded by molecular dynamics (MD) simulation and intermediate conformational ensembles were identified. The one and two-dimensional correlation spectrum was calculated for the intermediate and native states of the mini-protein. A direct structure-spectra relationship was determined by analysis of conformational properties and specific residue contributions. We identified the structural origin of diagonal and off-diagonal peaks in the 2DCS spectra for the native and intermediate conformational ensembles in the folding mechanism. This work supports the implementation of computational techniques in conjunction with experimental 2DCS to study the folding mechanism of proteins. In addition to exploring the folding mechanism the work presented here can be applied in combination with experiment to refine and validate current molecular dynamics force fields.PACS Codes: 87.15.Cc, 87.15.hm, 87.15.hp

New Insights into the Folding of a β-Sheet Miniprotein in a Reduced Space of Collective Hydrogen Bond Variables: Application to a Hydrodynamic Analysis of the Folding Flow

“…As has been shown in the previous works 29,30,37,38,43 , the Native, Cs-or, Ns-or, Ch-curl and Helical clusters correspond to the enthalpically stabilized basins on the FES, and all other, i.e., the unstructured conformations (see Table 1), form an “entropic” basin through which the former basins are kinetically connected. The distribution of clusters inside the entropic basin in Fig.…”

“…The list of the structured conformations is the same as in the previous studies 29,30,34–36,38,43 , but the clustering results are somewhat different, e.g., instead of single clusters for the native-like and Ns-or conformations 35,38 , two clusters for each of these conformations are observed. The present clustering is generally consistent with the results of Zheng et al 43 , where the FESs were constructed as functions of two collective variables (for details, see Supporting Information).…”

“…Ferrara and Caflisch 29 , and later Marai et al . 30 , have used the fractions of the native contacts formed in the N-terminal (residues 1–13) and C-terminal (residues 7–20) β -hairpins as the essential coordinates. Qi et al 31 performed an extensive analysis based on the genetic neural network (GNN) method of So and Karplus 32 to find optimum collective variables to describe the folding reaction.…”

Vibrational excitons in ionophores: experimental probes for quantum coherence-assisted ion transport and selectivity in ion channels

“…Cross-peaks in 2D spectra contain the relative orientation and coupling between vibrational dipoles which can be translated to a structure with a molecular model [31]. Amide I spectroscopy has proven particularly attractive because structure-based spectroscopic models exist that allow amide I IR spectra to be modeled from a protein structure [37,38,39]. For a proposed structure or pathway with atomistic structures, 2D IR data can be calculated and compared to the experiment to confirm or reject the proposed structure.…”

Exploring the Protein Folding Dynamics of Beta3s with Two‐Dimensional Ultraviolet (2DUV) Spectroscopy

“…The resulting multipoint correlation functions contain detailed structural and dynamics information. Studies so far have given some success in the IR, [12][13][14] near-IR, and visible spectral regions, however, extension to the UV domain is in its infancy. New, intense, and stable femtosecond lasers with high repetition rates allow multidimensional spectroscopy to be extended into the UV range.…”